doi:

DOI: 10.3724/SP.J.1145.2013.00941

Chinese Journal of Appplied Environmental Biology (应用与环境生物学报) 2013/19:6 PP.941-944

DNA-protein Crosslinks and Micronuclei Induced by Chronic Nitrogen Dioxide Inhalation in Rats


Abstract:
Nitrogen dioxide (NO2) is a ubiquitous reactive free-radical gas associated with momentary and chronic health effects. In the present study, chronic NO2 inhalation-induced effects on the DNA-protein crosslinks (DPC) and micronuclei (MN) in rats were investigated, by exposing Wistar rats to NO2 at 0.25 and 5 mg m-3. The results showed that chronic inhalation exposure of rats to NO2 not only induced the formation of DPC in cells of various internal organs (the brain, lungs, liver, spleen, kidneys and heart), but also resulted in obvious increase of MN frequency in the bone marrow cells of rats. Furthermore, the above responses showed signi fi cant linear dose-dependent manners. These results implicated that NO2 is a clastogenic and genotoxic agent, which may be an important reason for health problem induced by chronic inhalation exposure to NO2. Fig 1, Tab 1, Ref 22

Key words:nitrogen dioxide,rat,DNA-protein crosslinks,micronucleus

ReleaseDate:2015-04-15 08:42:19



[1] 孟紫强 . 环境毒理学 [M]. 北京: 中国环境科学出版社, 2000 [MengZQ. Environmental Toxicology [M]. Beijing: China EnvironmentalScience Press, 2000]

[2] Hochscheid R, Schuchmann U, Kotte E, Kranz S, Heinrichs S, MüllerB. NO2-induced acute and chronic lung injury cause imbalance ofglutathione metabolism in type II pneumocytes [J]. Med Sci Monit, 2005, 11: 273-279

[3] Ayyagari VN, Januszkiewicz A, Nath J. Pro-in fl ammatory responses ofhuman bronchial epithelial cells to acute nitrogen dioxide exposure [J].Toxicology, 2004, 197: 149-164

[4] Garn H, Siese A, Stumpf S, Wensing A, Renz H, Gemsa D. Phenotypicaland functional characterization of alveolar macrophage subpopulationsin the lungs of NO2-exposed rats [J]. Respir Res, 2006, 7: 4 doi:10.1186/1465-9921-7-4

[5] Sawa T, Ohshima H. Nitrative DNA damage in inflammation and itspossible role in carcinogenesis [J]. Nitric Oxide, 2006, 14: 91-100

[6] Jaiswal M, LaRusso NF, Nishioka N, Nakabeppu Y, Gores GJ. HumanOgg1, a protein involved in the repair of 8-oxoguanine, is inhibited bynitric oxide [J]. Cancer Res, 2001, 61: 6388-6393

[7] Hori M, Ishiguro C, Harashima H, Kamiya H. In vivo mutagenicities ofdamaged nucleotides produced by nitric oxide and ionizing radiation [J].Nitric Oxide, 2005, 28: 520-522

[8] Ohshima H, Sawa T, Akaike T. 8-nitroguanine, a product of nitrativeDNA damage caused by reactive nitrogen species: formation, occurrence, and implications in in fl ammation and carcinogenesis [J]. Antioxid RedoxSignal, 2006, 8: 1033-1045

[9] Walles SA, Victorin K, Lundborg M. DNA damage in lung cells invivo and in vitro by 1, 3-butadiene and nitrogen dioxide and theirphotochemical reaction products [J]. Mutat Res, 1995, 328: 11-19

[10] Shrivastava P, Pantano C, Watkin R, McElhinney B, Guala A, PoynterML, Persinger RL, Budd R, Janssen-Heininger Y. Reactive nitrogenspecies-induced cell death requires fas-dependent activation of c-JunN-terminal kinase [J]. Mol Cell Biol, 2004, 24: 6763-6772

[11] Han M, Guo Z, Li GK, Sang N. Nitrogen dioxide inhalation inducesgenotoxicity in rats [J]. Chemosphere, 2013, 90: 2737-2742

[12] Albertini RJ, Anderson D, Douglas GR, Hagmar L, Hemminki K, MerloF, Natarajan AT, Norppa H, Shuker DE, Tice R, Waters MD, Aitio A.IPCS guidelines for the monitoring of genotoxic effects of carcinogensin humans [J]. Mutat Res, 2000, 463: 111-172

[13] Zhitkovich A, Costa M. A simple sensitive assay to detect DNA-proteincrosslinks in intact cells and in vivo [J]. Carcinogenesis, 1992, 13(8):1485-1489

[14] Persinger RL, Poynter ME, Ckless K, Janssen-Heininger, YM.Molecular mechanisms of nitrogen dioxide induced epithelial injury inthe lung [J]. Mol Cell Biochem, 2002, 234-235: 71-80

[15] Chauhan AJ, Johnston SL. Air pollution and infection in respiratoryillness [J]. Br Med Bull, 2003, 68: 95-112

[16] Chauhan AJ, Krishna MT, Frew AJ, Holgate ST. Exposure to nitrogendioxide (NO2) and respiratory disease risk [J]. Rev Environ Health, 1998, 13: 73-90

[17] Tao Y, Huang W, Huang X, Zhong L, Lu SE, Li Y, Dai L, Zhang Y, ZhuT. Estimated acute effects of ambient ozone and nitrogen dioxide onmortality in the Pearl River Delta of Southern China [J]. Environ HealthPerspect, 2012, 120: 393-398

[18] Liu L, PoonR, ChenL, Frescura AM, Montuschi P, CiabattoniG, Wheeler A, Dales R. Acute effects of air pollution on pulmonaryfunction, airway in fl ammation, and oxidative stress inasthmatic children[J]. Environ Health Perspect, 2009, 117: 668-674

[19] Marks GB, Ezz W, Aust N, Toelle BG, Xuan W, Belousova E, CosgroveC, Jalaludin B, Smith WT. Respiratory health effects of exposure tolow-NOX un fl ued gas heaters in the classroom: a double -blind, clusterrandomized, crossover study [J]. Environ Health Perspect, 2010, 118:1476-1482

[20] Bermúdez E, Ferng SF, Castro CE, Mustafa MG. DNA strand breakscaused by exposure to ozone and nitrogen dioxide [J]. Environ Res, 1999, 81: 72-80

[21] G?rsdorf S, Appel KE, Engeholm C, Obe G. Nitrogen dioxide inducesDNA single-strand breaks in cultured Chinese hamster cells [J].Carcinogenesis, 1990, 11 (1): 37-41

[22] 肖永营, 夏锡荣, 施 毅, 童茂 荣, 张希龙 . SD大鼠二氧化氮吸 入性肺 损伤实验研 究 [J]. 医学研 究生学报, 2001, 14 (1): 15-17 [XiaoYY, Xia XR, Shi Y, Tong MR, Zhang XL. Changes of pulmonarymalondialdehyde, glutathione and total antioxidation content in SD ratwith nitrogen dioxide exposure [J]. J Med Postgraduate, 2001, 14 (1):15-17]